This renewal application deals primarily with the study of principles of organization and development in a CNS model, the cerebellum. The program (initiated in Norway in 1964 and funded by this agency since 1971) intends to refine quantitative and qualitative data on cerebellar circuitry (the mossy fiber-granule cell-Purkinje cell-cerebellar neurone system) using adult, developing and experimental animals, including certain murine mutants, and to contribute toward the bridging of the conceptual gaps that divide neurobiological information at three different levels of organization: system, cellular, and supramolecular. The actual research projects deal with continued studies on: 1) a fundamental module of cerebellar structure, namely the parallel fibers, including attempts to determine: their length in various animal species, their quantitative relations with Purkinje cells and with stellate and basket cells, their modifiability in experimental conditions (hormonal treatment), and the relations of cerebellar afferents (mossy and climbing fibers) to their parent cells. 2) the qualitative and quantitative features of synaptic projections of the cerebellar cortex on the cerebellar nuclei and their modification in mutant mice whose Purkinje cells either die ("nervous," "PCd") or undergo dystrophic changes ("quaking"). 3) the freeze-fracture features of the synapses, chemical and electrical, and of the neural processes in the mature and developing cortex. 4) the establishment of a peripheral model, the avian ciliary ganglion, in which the relationships between pre- and postsynaptic elements can be interfered with surgically. The methods include neurohistological stainings, electron microscopy, experimental neuroanatomy, morphometry and freeze-etching, of which the principal investigator and a small team of assistants have a first hand knowledge documented by several publications. The information sought will not only contribute to a better understanding of the role of the cerebellum in movement, but will also bring insight into the problem of how a specific neural circuit copes with the loss or the alteration of certain of its elements (plasticity). Companion studies on a peripheral model will enhance insight into the general biological laws which govern the development of the much diversified nervous tissues.